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Blood, 15 November 2002, Vol. 100, No. 10, pp. 3835-3837
BRIEF REPORT
Two distinct HLA-A0201-presented epitopes of the Wilms
tumor antigen 1 can function as targets for leukemia-reactive
CTL
Ilaria Bellantuono,
Liquan Gao,
Suzanne Parry,
Steve Marley,
Francesco Dazzi,
Jane Apperley,
John M. Goldman, and
Hans J. Stauss
From the Departments of Immunology and Haematology,
Faculty of Medicine, Imperial College, Hammersmith Hospital, London,
United Kingdom.
Using the allo-restricted T-cell approach to circumvent tolerance,
we have previously identified a cytotoxic T-lymphocyte (CTL)
epitope in the transcription factor Wilms tumor antigen 1 (WT1)
presented by HLA-A0201 (A2) class I molecules. Here we describe
an additional A2-presented epitope and show that CTLs against
both epitopes kill WT1-expressing leukemia cell lines. Colony-forming
assays demonstrated that both types of CTL killed CD34+
progenitor cells from A2+ leukemia patients, but not from
A2+ healthy individuals. The long-term culture-initiating
cell (LTC-IC) assay was used to analyze the killing activity of
WT1-specific CTLs against the more immature fraction of
CD34+ cells. The CTLs killed LTC-ICs of patients with
chronic myelogenous leukemia (CML), whereas the function of
normal CD34+ progenitor/stem cells was not inhibited.
Together, the data show that CTLs specific for 2 distinct peptide
epitopes of WT1 can discriminate between normal and leukemia LTC-ICs,
suggesting that such CTLs have the potential to selectively kill CML
progenitor/stem cells.
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